New insights into immunity to skin fungi shape our understanding of health and disease

Abstract

Fungi represent an integral part of the skin microbiota. Their complex interaction network with the host shapes protective immunity during homeostasis. If host defences are breached, skin-resident fungi including Malassezia and Candida, and environmental fungi such as dermatophytes can cause cutaneous infections. In addition, fungi are associated with diverse non-infectious skin disorders. Despite their multiple roles in health and disease, fungi remain elusive and understudied, and the mechanisms underlying the emergence of pathological conditions linked to fungi are largely unclear. The identification of IL-17 as an important antifungal effector mechanism represents a milestone for understanding homeostatic antifungal immunity. At the same time, host-adverse, disease-promoting roles of IL-17 have been delineated, as in psoriasis. Fungal dysbiosis represents another feature of many pathological skin conditions with an unknown causal link of intra-and interkingdom interactions to disease pathogenesis. The emergence of new fungal pathogens such as Candida auris highlights the need for more research into fungal immunology to understand how antifungal responses shape health and diseases. Recent technological advances for genetically manipulating fungi to target immunomodulatory fungal determinants, multi-omics approaches for studying immune cells in the human skin, an

Mechanisms of pathogenicity for the emerging fungus Candida auris

“…Mycobiomes with shared dominance by a variety of Candida species switched to a singular dominance by C. auris 30% to 50% of the time. These data highlight the importance of studying Malassezia species during interactions within the skin microbiome (reviewed in [40]). The group also examined bacterial communities and identified organisms with higher abundance in C. auriscolonized patients (Proteus mirabilis, Klebsiella pneumoniae, Providencia stuartii, and Pseudomonas aeruginosa).…”

“…auris 30% to 50% of the time. These data highlight the importance of studying Malassezia species during interactions within the skin microbiome (reviewed in [ 40 ]). The group also examined bacterial communities and identified organisms with higher abundance in C .…”

Epidermal barrier impairment predisposes for excessive growth of the allergy‐associated yeast Malassezia on murine skin

“…[7][8][9] Due to the lack of fatty acid synthase and the consequent dependence on exogenous lipids, Malassezia is highly adapted for life on the mammalian skin, where it finds favorable conditions in lipid-rich areas such as sebaceous hair follicles. 10 Malassezia is tightly controlled by the cutaneous immune system, which by means of IL-17 mediated immunity prevents fungal overgrowth [11][12][13] and thereby ensures homeostatic colonization. 14 How immunosurveillance of the commensal fungus is affected under conditions of inflammation and barrier disruption in diseased skin is however not well understood.…”

“…Of the 20 Malassezia species described so far, M. restricta and M. globosa dominate human skin, followed by M. sympodialis and M. furfur , while M. pachydermatis is the most abundant species on canine skin 7–9 . Due to the lack of fatty acid synthase and the consequent dependence on exogenous lipids, Malassezia is highly adapted for life on the mammalian skin, where it finds favorable conditions in lipid‐rich areas such as sebaceous hair follicles 10 . Malassezia is tightly controlled by the cutaneous immune system, which by means of IL‐17 mediated immunity prevents fungal overgrowth 11–13 and thereby ensures homeostatic colonization 14 .…”

Epidermal barrier dysregulation in atopic skin predisposes for excessive growth of the allergy-associated yeastMalassezia

“…Given its dependence on exogenous lipids due to the lack of fatty acid synthase, Malassezia finds favorable conditions in lipid-rich areas of the skin such as sebaceous hair follicles. 29 By metabolizing skin lipids for its own benefit, the fungus contributes to the lipid balance of the cutaneous niche. In turn, Malassezia is tightly controlled by the cutaneous immune system, which prevents fungal overgrowth.…”